Abstract: Objective: To explore the evidence-based nursing optimization strategy for catheter tip positioning during peripherally inserted central catheter (PICC) insertion in patients with persistent left superior vena cava (PLSVC). Methods: For one ovarian cancer patient with PICC malposition in the coronary sinus (CS) due to PLSVC, multi-modal imaging techniques were integrated to accurately locate the catheter tip. The catheter position was adjusted based on evidence (withdrawing 5 cm), and a standardized nursing process was established, including personalized health education, catheter fixation and displacement monitoring, complication monitoring, establishment of a specialized disease information archive system, and formulation of a follow-up plan. Results: The catheter tip was successfully withdrawn from the coronary sinus (at the T8 level) to the middle and lower part of the PLSVC (at the T6 vertebral level), and the catheter functioned normally after adjustment. No complications such as arrhythmia or thrombosis occurred during the 332-day chemotherapy period. Conclusion: The PICC tip in PLSVC patients should be positioned in the middle and lower part of the PLSVC (at the T5–T7 vertebral level). This new standard can effectively avoid CS-related complications. The integration of multi-modal imaging techniques and evidence-based nursing management are key to ensuring safe infusion.